Many animals possess a coelomic cavity which separates the gut from other structures. Peritoneum, like pleura and pericardium, is a derivative of the coelomic cavity. In the most primitive of animals, consisting only of a cylindrical body wall containing a tubular gut, separation of the two parts by a non-stick derivative of the coelomic cavity is essential if peristalsis is to maintain a flow of nutrition from one end of the gut to the other. Abolition of peristalsis through adhesion of gut to body wall is incompatible with life, thus from the earliest of evolutionary time, provision of a non-stick surface between these vital structures has been imperative. In man, peritoneal adhesions resulting from any cause, whether due to surgery, chronic organismal inflammation or endometriosis, expose the individual to dire consequences.
In primitive animals, the coelomic cavity is under constant and serious threat from ingress of organisms or noxious molecules from the external environment, either through the gut or body wall. The danger to life is rapid, as is the unobstructed spread of an invader throughout the entire coelom. Thus, an immediate defensive response evolved whereby the cavity fluid thickens to prevent leakage and entrap invading organisms. This event is achieved by polymerization of a soluble protein (proto-fibrinogen) into a voluminous network. Medical science and biology in general remain largely ignorant of the primordial site and purpose of the elaborate and now highly evolved mechanism of clotting in the vascular systems of higher vertebrates. This has resulted in a failure to perceive that this system of clotting evolved in tandem with another equally life maintaining system of non-stick properties of the lining surfaces of the coelomic cavity, which is the recently discovered lamellar bodies secretory system. The vast bulk of research into the clotting mechanism is almost entirely vasculo-centric and hitherto lack of research into the clotting mechanism in serous cavities has resulted in failure to recognize the crucial role of the lamellar body system in the gelation of fibrin throughout the entire body.
Post Operative Surgical Adhesions
It is widely recognized in the surgical community that peritoneal adhesions are an extremely common complication of abdominal and pelvic surgery, giving rise to significant morbidity, mortality and unwanted loss of operating time and expense to health services throughout the world. However, until recently, lack of good epidemiological data, combined with an inability to effectively prevent adhesion formation, has limited the impetus to carry out serious investigation of this disorder.
In the developed world, the most common cause of peritoneal adhesions is abdominal surgery, where the main cause of small bowel obstruction is adhesion formation following previous surgery. Indeed, throughout this century there has been a continual rise in the cases of intestinal obstruction due to adhesions, from 7% in 1930 to 64% in 1969, which reflects the increasing frequency of abdominal surgery in the population at large. It is now recognized that adhesions are responsible for a significant morbidity, loss of work and expense to health services world-wide. With the recent development of minimally invasive surgery, it was hoped that adhesions would be a thing of the past. However, this has not been the case.
A recent epidemiological study has provided accurate and detailed statistics on the incidents of adhesions, giving evidence of the seriousness of the problem. This study was carried out by the Surgical and Clinical Adhesions Research (SCAR) Group using validated data from the Scottish National Health Service medical record linkage database. It identified patients undergoing abdominal or pelvic surgery in 1986 who had no record of surgery in the preceding five years. Patients were then followed for ten years and subsequent re-admissions were reviewed and outcomes classified by the degree of adhesion. 5.7% of all re-admissions were classified as being caused incontrovertibly by adhesions. A further 28.9% were readmitted with signs and symptoms of sub-acute obstruction believed to be most probably caused by adhesions. In Scotland in 1994, a total of 4,199 admissions for a population of 5 million were directly related to adhesions. (Ellis H, Moran B J, Thompson J N et al. Adhesion-related hospital re-admissions after abdominal and pelvic surgery: A retrospective cohort study. Lancet. 1999;353;1476-1480). These figures highlight a remarkable scale of adhesion related admissions, when compared to similar figures of other common, essential surgical procedures, such as hip replacement operations (4,394), coronary artery bypass grafts (4,020) or haemorrhoid surgery (4,226) during the same time period and the same population.
A further effect of adhesions is the difficulty and time taken to dissect them before proceeding with an operation. A study of workload involved for 120 patients undergoing a re-operative laparotomy estimated a mean increase of 24 minutes in the total time of the operation because of intra abdominal adhesions from previous surgery. There is also an intra operative danger of adhesiolysis (lysis of adhesions), as was demonstrated in 274 patients undergoing re-laparotomy where a 21% risk of bowel perforation was identified.
With respect to mortality, intestinal obstruction is the most severe consequence of adhesions. It has been shown that of patients who require abdominal re-operation, 30% to 41% have adhesion related intestinal obstruction.
It should be noted that the clinical consequences of adhesions are not simply confined to the gut. Adhesions are the leading cause of secondary infertility in women, and are responsible for substantial abdominal and pelvic pain and discomfort.
In fact, surgical adhesions are known to cause problems in a range of areas. The following types of surgery can result in surgical adhesions, which cause a number of problems; abdominal, thoracic (including both cardiac and pleural), spinal, intra-cranial, intra-ventricular, intra-placental, urological including both gynecological and fertility which can occur during fallopian tube surgery, urinary tract surgery, IVF treatment and during reversal surgery in the vas deferens), orthopedics, arthroscopy, ear, nose and throat, neurological (including peripheral nerve surgery and spinal microsurgery), cardiology and radiology.
The incidence of post-operative adhesions is becoming increasingly unacceptable to healthcare communities throughout the world. However, recent advances in the molecular biology of serous cavities have at last provided accurate information on the aetiopathogenesis of adhesions, which allows evidence based strategies for their prevention during any surgical procedure in any of the derivatives of the coelomic cavity. These new preventative measures involve an understanding of the formation and removal of fibrin in serous cavities. Current knowledge presumes that the only factors are molecular and cellular elements involved in fibrin gelation and fibrinolysis. In the current invention it can be seen that the secretion of lamellar bodies plays a key role in both the physical structure of fibrin deposition and the speed and extent of its removal. The current invention utilizes this knowledge to provide therapeutic uses of lamellar body solutions.
The Role of Fibrin in the Acute Inflammatory Response
Fibrinogen is an acute phase, soluble protein, which increases in the blood and tissue fluids temporarily as a consequence of inflammatory reactions. Contact with pro-coagulant factors causes polymerization of fibrinogen to form a fibrinous gel.
At the beginning of the 20th Century, pathologists described and defined the sequence of events in the acute inflammatory response. The reactive changes involved three sequential processes:    1. changes in vascular caliber and blood flow    2. increased vascular permeability and the formation of protein rich inflammatory exudate    3. escape of leucocytes from vessels into extravascular tissue spaces
An initial event in the tissue spaces is the appearance of fibrin identified by a variety of histochemical techniques. Early histological studies recognized that fibrin represented an attempt to wall-off the infected or damaged area, as well as providing a “scaffolding” of fibers in the turgid edematous tissue to assist the amoeboid movement of inwardly migrating leucocytes. When looking at acute inflammatory response, an early and orderly disappearance of fibrin heralded a successful outcome to the inflammatory response, as the excess tissue fluid drained away into the lymphatics and the fibrin scaffolding was dismantled.
Thus, the optimal result of an acute inflammatory response is complete restitution of the normal structure and function of the affected tissue. This process is referred to as resolution or healing by first intention. In the process of resolution, the primary task is the removal of cellular debris and fibrin. If, however, heavy deposits of fibrin are formed during the early stages of acute inflammation, they may not be removed completely within a few days by the fibrinolytic enzymes of the inflammatory exudate. The consequence of this failure can be profound, as fibrin which is not rapidly removed undergoes a process called organization. Macrophages migrate into the fibrin, closely followed by ingrowth of new capillaries and fibroblasts to form a tissue known as granulation tissue. As granulation tissue matures, it is eventually replaced by a firm, dense, fibrous tissue more commonly referred to as scar tissue. Where granulation tissue between two opposing tissue surfaces or organs is transformed by this process, the dense fibrous tissue joining the previously separate entities is referred to as an adhesion. This process is also known as healing by second intention and the adhesions may seriously compromise normal function at the site of the original acute inflammatory response.
In the pre-antibiotic era, the clinical signs and symptoms of fibrinous exudates in response to bacterial infections formed the bulk of everyday medical practice. The sound of a friction rub heard on auscultation of the chest signified a thick fibrinous exudate, the acute inflammatory response of the pleura to underlying pulmonary infection, as in pneumococcal pneumonia. Pericardial friction rubs were also commonplace, not only in response to diverse infections, but also in uremia and rheumatic fever. With the complete disappearance of many disease types as medicine advanced, the previously recognized role of fibrinous deposition in most diseased states was not appreciated by the current generation of researchers. An exception to this rule has been molecular biologists working in the field of rheumatoid disorders, where the grossly incapacitating effect of conversion of extravascular fibrin deposits to dense fibrous tissue remains a focus of ongoing research.
Also, this type of post-inflammatory adhesion can be seen in peritonitis, pericarditis, joint disease (for example in cases of post-rheumatoid arthritis and severe gout), CNS disease (including meningitis), ear, nose and throat diseases, gynecological disease (such a chlamydia which attracts fibrin deposition) and urology.
In the last two decades there has been considerable advances in the molecular biology of mesothelium, its reaction to injury and inflammation and its repair and regeneration. A thin mesothelial monolayer resting on a basement membrane covers all of the abdominal organs (visceral) and the wall of the abdominal cavity (parietal). In an adult, its surface measures up to 2 m2, presenting a large area which acts as a semi-permeable membrane for the exchange of water and small molecular weight solutes. The human peritoneal cavity exists in normal life as a potential space with the opposing surfaces being separated by only 5μ. It therefore contains no more than 50 ml of clear, sterile fluid with a low specific gravity and low protein content. Fibrinogen is not present and therefore serous fluid will not clot.
The local inflammatory response of the peritoneum is similar to other tissues, but the peritoneal lining is unique in that it presents a large exudative and absorptive surface. The lining can separate to accommodate many liters of fluid. At sites of irritation there is an outpouring into the peritoneal cavity of fluid with a high protein content. This exudate contains fibrinogen which polymerizes to solid fibrin on contact with local tissue factor released by mesothelium or leucocytes. Plaques of fibrinous exudate forming on the inflamed surface glue adjacent bowel, mesentery and omentum to each other. The process of adhesion is greatly facilitated by the inhibition of peristalsis which allows loops of bowel and omentum to lie undisturbed while the highly adhesive fibrin progressively walls-off the damaged area. Although this process has evolved to localize infection and halt its spread through the entire peritoneal cavity, the same response inevitably occurs when the peritoneum is surgically opened under sterile conditions.
Thus, as part of the inflammatory response, the mesothelium has a powerful pro-coagulant ability through its local production of tissue factor. This, when released into the peritoneal exudate, initiates a cascade leading to the polymerization of fibrinogen to solid fibrin. This is balanced by an equally powerful fibrinolytic capability where normal peritoneal tissues contain measurable levels of plasminogen which can be converted to plasmin by the secretion of tissue plasminogen activator. These processes constitute cascade systems finely balanced by activators and inhibitors.